Anti-CGRP monoclonal antibodies for prevention of migraine

This article includes discussion of anti-CGRP monoclonal antibodies for prevention of migraine, anti–calcitonin gene-related peptide monoclonal antibodies for prevention of migraine, anti-CGRP MAbs, eptinezumab, erenumab, fremanezumab, galcanezumab, and monoclonal antibodies for migraine. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

• The rationale for this approach is based on the role of CGRP in the pathogenesis of migraine.

• Three of the 4 MAbs in development (eptinezumab, fremanezumab, and galcanezumab) target CGRP itself, whereas the fourth, erenumab, targets CGRP receptor.

• Clinical trials have shown the efficacy and safety of anti-CGRP MAbs in reducing migraine attacks.

• Erenumab is expected to gain regulatory approval in 2018.

Historical note and terminology

Most preventive treatments for migraine are nonspecific, and their efficacy and safety are often unsatisfactory. Some monoclonal antibodies (MAbs), which target calcitonin gene-related peptide (CGRP) receptor or CGRP itself, are in development for migraine prophylaxis. CGRP is a neuropeptide that, along with its receptor, is found in both central and peripheral neurons and influences both neuronal modulation of pain as well as vascular activity (Edvinsson 2017; Iyengar et al 2017).

CGRP receptor (CGRP-R) is also a target for drugs for acute migraine attacks. Gepants, another CGRP-R antagonist class, are a new nonvasoconstrictive approach in the acute treatment of migraine. When compared with triptans, gepants show a similar efficacy profile. However, results of clinical trials of gepants have not been encouraging for their use in clinical practice. Some were discontinued during development due to concerns for hepatotoxicity or for unknown reasons. Clinical trials of other gepants for acute migraine continue but will not be discussed in this article.

Four anti-GRCP MAbs are in clinical trials and will be described in this article. The focus of this article will be on erenumab, the most advanced of these, which is in the development and approval process.

• Erenumab. License applications for erenumab were submitted to the U.S. Food and Drug Administration and the European Medicines Agency in Europe in May/June 2017 (Giamberardino et al 2016; Giamberardino et al 2017). It is expected to be approved in 2018.

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